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The severity of ankylosing spondylitis and responses to anti-tumour necrosis factor biologics are not influenced by the tumour necrosis factor receptor polymorphism incriminated in multiple sclerosis

Genes & Immunity (2018) | Download Citation

Abstract

Genetic polymorphism (rs1800693) of TNFRSF1A (type 1 tumour necrosis factor receptor) encodes a potentially anti-inflammatory soluble truncated form of the p55 receptor, which is associated with predisposition to multiple sclerosis but protection against ankylosing spondylitis (AS). We analysed 2917 UK Caucasian cases by linear and logistic regression for associations of rs1800693 with disease severity assessed by the Bath Ankylosing Spondylitis measures of disease activity and function (BASDAI, BAS-G and BASFI) and/or responses to anti-TNF therapy. In contrast to predictions, rs1800693 GG homozygotes actually had significantly worse BASDAI (mean 4.2, 95% CI: 4–4.5) than AA homozygotes (mean 3.8, 95% CI: 3.7–4) in both the unadjusted (difference = 0.4, p = 0.006) and adjusted analyses (difference = 0.2–0.5, p = 0.002–0.04 depending on the adjustment model). We found no evidence that rs1900693 predicted functional status (BASFI) or global disease scores (BAS-G), and it exerted no influence on either the intention to treat with or efficacy of anti-TNF treatment.

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Acknowledgements

We wish to thank all the study participants who generously donated their DNA to this study. MV was funded by the NIHR Oxford Comprehensive Biomedical Research Centre (immunity and inflammation theme A93081) and Arthritis Research UK (grant 21428). ARR was funded by Arthritis Research UK (grant 20402). Additional funding was provided by Arthritis Research UK (18797, 19536, 20402, 20796), the NIHR Thames Valley collaborative research network and National Ankylosing Spondylitis Society (UK).

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Affiliations

  1. National Institute for Health Research Oxford Comprehensive Biomedical Research Centre, Oxford, UK

    • Laura Watts
    • , Tugce Karaderi
    • , Amity Roberts
    • , Louise Appleton
    • , Tom Wordsworth
    • , Carla Cohen
    • , Paul Wordsworth
    •  & Matteo Vecellio
  2. National Institute for Health Research Oxford Musculoskeletal Biomedical Research Unit, Oxford, UK

    • Laura Watts
    • , Tugce Karaderi
    • , Amity Roberts
    • , Louise Appleton
    • , Tom Wordsworth
    • , Carla Cohen
    • , Paul Wordsworth
    •  & Matteo Vecellio

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The authors declare that they have no conflict of interest.

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Correspondence to Matteo Vecellio.

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DOI

https://doi.org/10.1038/s41435-018-0017-0